Should we regulate people’s access to their own genome data?

Should the public have full access to information about their genomes, even if …

Back in June, the US Food and Drug Administration fired a warning shot across the bow of the nascent direct-to-consumer (DTC) genetic testing industry. The FDA felt that some of the services were marketing their products as medical tests, and therefore had to provide evidence of their efficacy. Since then, both Congress and the Government Accountability Office have looked into the DTC market, raising the prospects for direct government intervention in the market.

On the most basic level, government intervention in this market has the scent of an invasion of privacy. Shouldn't any citizen have the right to know about the contents of his or her own genome? But it's difficult to separate that basic level of knowledge from the medical implications it has, which is where safety, accuracy, and privacy issues—and government enforcement of them—come in.

Known errors and unknown interpretations

Currently, genetic tests generally involve what are called SNP arrays, for single nucleotide polymorphisms. There are many sites in the human genome that we know commonly vary from person to person. It's possible to design a DNA chip that contains these sequences, which can be used to determine which variants an individual has; careful analysis of this same data can provide an indication of whether some portions of the genome have an extra copy, or are missing one as well.

All of this is standard laboratory technique. But, like anything else done in the lab, these tests have known error rates and can vary based on the precise chip used for the analysis (they're available from a number of different manufacturers). Some of this error may appear as missing data, but there's always the potential for making the wrong call. It's tempting to think this is a temporary issue—the era of cheap genome sequences appears to be just around the corner. But full sequencing has its own errors, with most "completed" genomes having a set of gaps and areas of poor sequence coverage.

So, even if we accept that people should have unfettered access to their genomic information, that access would need to come with a serious disclaimer: some of the information is probably wrong, and doesn't reflect what's actually in our genomes.

Interpreting even accurate data, however, can be a challenge. For some issues, like sickle cell anemia, matters are simple: a specific base change causes the disease. In others, it's more complex. Huntington's Disease is caused by a single gene, but the onset and severity vary based on the extent of the damage to the gene. In the fast-paced world of biomedicine, however, these cases are the exceptions. In most cases, genetic features end up linked to small risks—a 15 percent greater chance of heart problems, for example—and is simply part of a large confluence of risk factors scattered throughout the genome (which then interact with environmental risks).

Explaining risk

All of this puts a high burden on the genetic testing companies, given that large parts of the public don't have a good grasp of concepts like experimental error and risk probabilities. But the recent news for genetic testing companies has suggested that some of them aren't exercising the diligence they should be.

The initial letters from the FDA clearly indicate that the agency has found some of the companies promoting their services as capable of providing medically relevant diagnostic information. But that paled in comparison to some of the issues turned up by the GAO. Its undercover use of a number of services turned up a few that appeared to be little more than scams. Even the best services had problems, however, with some employees overpromising when it came to results, and others providing potentially misleading information. (The Genomics Law Report has an excellent summary of the hearings that followed the release of the GAO report.)

The response to the hearings has been pretty varied, although nearly everyone agreed that they probably meant bad things for the nascent industry. At one extreme, advocates of personal genomics are now worried that paternalistic regulations will keep consumers from their genomic information, and argue that the consumers themselves should ultimately decide how this information is used.

More moderate voices seem to accept that some form of regulation is going to be necessary. In an opinion piece in today's Nature, Gail Javitt of the Johns Hopkins Institute of Bioethics argues that the problems with genetic tests—difficult to quantify errors and risks—are actually typical of a lot of recent medical advances, and a more general framework for certifying the accuracy of both testing and the information provided to the public would have benefits well beyond the issues highlighted by the Congressional hearings.

In an accompanying editorial, Baylor's Andrew Beaudet argues for a similar approach to the actual testing, but differs greatly when it comes to informing the public. In Beaudet's view, discussions of the implications of genetic testing are inherently medical, and the process of testing needs to be limited to medical practitioners with relevant training. DTC services would effectively be banned.

Given that both the FDA and Congress appear to have their hands full with other issues, there's a good chance that any formal regulation will take several years to develop. There's always the chance that, during that time, some portion of the public will educate itself on the issues involved, and actually add its voice to those of the businesses and regulators with a stake in any decisions. Of course, if a sufficient fraction of the public educated itself, then the need for careful regulation would be greatly reduced.

The contents of my genome are a simple sequence of base pairs. Certainly you can argue that I have a right to that basic data, but that's not what these "services" provide. They provide interpretation of the data that they are in many cases not competent to perform, so it's essentially fraud.

I'm sorry if this is a tangent, but I really think if we actually educated our population, these kinds of things wouldn't really be as much of a problem. You're always going to need to go after the scammers, but hell... if the whole country thinks there's a single gene for getting heart attacks and a single gene for getting cancer and a gene for being depressed and a gene for liking orange pants and a gene for becoming a rich and famous actress, it's going to be very hard to keep them from jumping to conclusions no matter how you regulate.

"All of this puts a high burden on the genetic testing companies, given that large parts of the public don't have a good grasp of concepts like experimental error and risk probabilities"

A person is free to adjust their patterns of behavior according to a wide range of factors of their own choosing. They are also free to engage in a variety of behaviors of their own choice. There will never be any limitation on people getting their own DNA tested if they want to. Concievably there might be some requirement for testing compnaies to warn about potential error rates. But nothing more. Any treatment that has substantial effects on a person's health requires an MD. If MD's use genetic tests as a basis for deciding on treatments, there well could be some kind of standards to insure accuracy of the tests.

While I can see there are obvious issues with DTC genomic testing, I'm with naphini on this one. Educate the people getting scammed and it will be harder for them to get scammed again. Stop one scammer and another one just starts up. I mean come on, how many homeopathic practitioners are there in north america? It's the whole teach someone how to fish instead of just giving them a fish.

I'd say I'm fairly educated in that field (at least enough not to get mislead by such companies) and I would be outraged if I wanted to see my genome but was stopped by a government regulation. Having said that, at this point it would probably only be a novelty for me.

So... I'll have more rights to my credit report than to my GNOME data?

No, and this is a common falacy among the hardcore genetic libertarians out there. No one is saying you can't have access to your data. If you just wanted to pay Complete Genomics (for example) the $11k or so it costs to sequence your genome and just have them give you back the results with no interpretation, the FDA wouldn't give a fig. They also don't care about 23andMe telling you that you have the gene for dry earwax or curly hair or that you can smell asparagus in your urine.

What they do care about are companies making medical claims. If you want to sequence someone's DNA, or analyze their sequence data, and then tell that person that they have disease risks, that is very clearly medicine, and that is regulated by law, and has been since 1906.

The problem is that the DTC companies have wanted to have their cakes and eat them. They claim their tests are not medical, and then offer BRCA or APOE status, as well as reporting on predispositions for chronic multigenic diseases. Except for the multigenic diseases, you get 3 different answers from 3 different companies, and despite their claims several years ago that they were working together on industry standards, none exist. And that's where FDA comes in.

DTC genomics as we currently know it is on the way out, if you ask me. Why would you pay someone $400 for a gene chip assay that won't tell you anything about rare variants, novel mutations, CNVs, indels etc when affordable whole genome sequencing is 2-4 years away? It would be like buying a walkman when you know that the iPod is about to come out.

Any treatment that has substantial effects on a person's health requires an MD. If MD's use genetic tests as a basis for deciding on treatments, there well could be some kind of standards to insure accuracy of the tests.

Which is what some of them are doing, by looking at CYP450 genes and giving their customers pharmacogenomics advice. Without FDA approval.

I think the burden must be placed on the companies. Yeah, sure, let them print out your code and give it to you—but let’s make sure that they have a validated process (and equipment and software!) to provide this good.

Let’s also make sure they’re not giving advice or interpretations they have no business giving. If a firm takes on geneticists qualified to interpret (parts of) genetic sequences—great! If not, then they can’t offer the service.

Either way, the firm needs to provide a guarantee of the efficacy of their product.

The contents of my genome are a simple sequence of base pairs. Certainly you can argue that I have a right to that basic data, but that's not what these "services" provide. They provide interpretation of the data that they are in many cases not competent to perform, so it's essentially fraud.

Agreed. It's a sensational title, but what's really being regulated is the medical value of the testing.

What they do care about are companies making medical claims. If you want to sequence someone's DNA, or analyze their sequence data, and then tell that person that they have disease risks, that is very clearly medicine, and that is regulated by law, and has been since 1906.

What's the difference between telling their customers they have disease risks, or prefixing their statements with "Studys have shown that having/not having this gene..."?

Since I'm cited as the "extreme" advocate of personal genomics in John's post, I feel obliged to step in and note that none of us are arguing that this industry should go entirely unregulated - rather, the discussion is about the balance between consumer protection on one side and the stifling of innovation and educational opportunities on the other.

In fact DTC genomics is already subject to regulation: testing laboratories in the US must comply with the same CLIA certification for quality control standards applied to clinical labs, and the companies are also (theoretically) bound by laws regarding false advertising and unethical marketing. Even us "genetic libertarians" agree that these regulations must be enforced (and indeed strengthened) in order to weed out the scammers at the more disreputable end of the DTC menagerie.

We also believe that the industry should be forced towards greater transparency: companies should be required to register the markers they test, the algorithms they use to predict risk, and the evidence supporting their parameter values in a public database (such as the NIH's proposed Genetic Testing Registry). A more open marketplace supports informed consumer decisions, and this would also allow easier criticism of inaccurate tests by experts (who, in general, are better placed to evaluate the merits of these complex tests than FDA bureaucrats).

Beyond that, we are concerned that the blatantly overblown rhetoric of the FDA (which has threatened to regulate these tests as "high risk" medical devices, and spread out-of-context anecdotes about the potential harms of genetic testing) may translate into excessive, paternalistic regulation that will stifle innovation in the industry and reduce people's ability to learn from their own genomes.

Regulatory approaches should be guided by the potential harm of a test, not by some outdated and arbitrary division between "medical" and "non-medical" results. Right now the available evidence suggests that the real harm caused by DTC genetic testing - for all the scare-mongering from the FDA - is close to nil. So by all means let's ensure that the results provided by companies are accurate and comprehensible, and that scammers making false claims are punished; but let's do this in a careful, sensible way, making sure that the costs of each new regulatory measure are justified by a genuine need to protect consumers.

So... I'll have more rights to my credit report than to my GNOME data?

No, and this is a common falacy among the hardcore genetic libertarians out there. No one is saying you can't have access to your data. If you just wanted to pay Complete Genomics (for example) the $11k or so it costs to sequence your genome and just have them give you back the results with no interpretation, the FDA wouldn't give a fig. They also don't care about 23andMe telling you that you have the gene for dry earwax or curly hair or that you can smell asparagus in your urine.

What they do care about are companies making medical claims. If you want to sequence someone's DNA, or analyze their sequence data, and then tell that person that they have disease risks, that is very clearly medicine, and that is regulated by law, and has been since 1906.

The problem is that the DTC companies have wanted to have their cakes and eat them. They claim their tests are not medical, and then offer BRCA or APOE status, as well as reporting on predispositions for chronic multigenic diseases. Except for the multigenic diseases, you get 3 different answers from 3 different companies, and despite their claims several years ago that they were working together on industry standards, none exist. And that's where FDA comes in.

DTC genomics as we currently know it is on the way out, if you ask me. Why would you pay someone $400 for a gene chip assay that won't tell you anything about rare variants, novel mutations, CNVs, indels etc when affordable whole genome sequencing is 2-4 years away? It would be like buying a walkman when you know that the iPod is about to come out.

It's also interesting to note how blood tests are handled. Unlike a genetics test, a civilian is not allowed to just walk into a blood center, like Carter Blood Care, and request a blood panel. Those require a doctor's authorization. However, you can get a genetics test without a doctor's authorization. So there's one difference.

Let's say you got a doc's auth and got the blood test done. You have complete access to the blood test results, but they won't make much sense without the doc helping to interpret. And then, the doc is the one who's usually most qualified to recommend a course of action based on the results.

The problem is that the same SHOULD be true for a genetics panel. But it's not. Some of these genetics companies start making suggestions, like taking supplements to curtail Homocysteine overloads since you have genetic markers indicating you're a candidate for Homocysteine overload.

I'm of the mind-set that doctor's should be the ones helping you interpret genetic panels, not the company that runs the panel. It's the same way with getting a sonogram. You have a tech who does the test, but they're not allowed to tell you anything about what they see...they're supposed to pass the results over to your doc for his analysis.

The problem here is that there are still too many doctors indoctrinated in the "pop this pill" pharmaecutical school of medicine. Genetics is still fairly new, panels are expensive, and a lot of doctors are uncomfortable with interpreting them or thinking of them as a reliable tool of diagnosis. So, it has yet to integrate greatly into the medical field as a useful tool.

Another hitch is that the docs that tend to put more emphasis on genetic panels tend to be Naturopaths, who focus on natural solutions, like dietary changes, vitamin supplements, etc. Naturopaths are sort of seen as "psuedo-doctors", and not taken as seriously as "real" doctors. So, since Naturopaths use genetic panels more, cross-comparing them to amino acid & vitamin/mineral panels, it just makes other doctors think genetic panels are just another hoaky tool those "crazy Naturopaths" use. It drops the credibility some.

Much like Congress, you have to wait for the old fart doctors on the major medical boards to eventually pass the torch on to doctors who are more interested in the cutting science.

How about we just say that anyone who wants info on their genome is free to find it themselves. How hard can it be to learn to sequence your own DNA?

If you're in a university dept or research institute with a pyrosequencer, such a provided by 454 Life Sciences, you can generate 400 million nucleotides worth of sequence data in about 12 hours, at a consumable cost of around $10k. For reference, the haploid human genome is around 3bn nucleotides.

Of course, you're VERY unlikely to find a researcher who's willing to do this for you, unless part of a bona fide study with the proper ethical clearance. Personally I'm happy not knowing what lurks in my genome.

<i>DTC genomics as we currently know it is on the way out, if you ask me. Why would you pay someone $400 for a gene chip assay that won't tell you anything about rare variants, novel mutations, CNVs, indels etc when affordable whole genome sequencing is 2-4 years away? It would be like buying a walkman when you know that the iPod is about to come out.</i>

For the same reason people buy an iPhone 4 now, even though they know there will be a new generation (with better antennae) some time next year. I'm genuinely confused about why you see this as a useful argument.

A more expanded response: understanding genetic information is hard, but the more time you spend immersing yourself in the world of SNPs, odds ratios and relative risks the easier it gets. People who buy a genome scan now, and spend a little time digging around in their results, will have a head-start in terms of genetic literacy by the time whole genome sequences become available.

Alternatively, you could just sit back and wait 2-4 years for your genome, and then hope your doctor is one of the tiny fraction of medical practitioners who will actually have the faintest clue what to do with the information it contains. Good luck with that.

What a stupid & inflammatory article title. Ars, you are really pushing it. When I received the page, there was an advert from Wired on the top. I am going to refrain from visiting Wired for the rest of the month.

Of course a person's right to their own genome should not be regulated. That's idiotic.

However, companies that do genome sequencing probably should be regulated on some or all of the following grounds:* ability to avoid contamination from other DNA sources* ability to produce a complete and accurate genome* truthfulness regarding what hereditary conditions can or cannot be detected* truthfulness regarding what 3rd parties will or will not have access to the data

"....Any treatment that has substantial effects on a person's health requires an MD. If MD's use genetic tests as a basis for deciding on treatments, there well could be some kind of standards to insure accuracy of the tests.

If you are talking about stuff like breast removal, sure--that will require an MD. But there's another side to that: if people don't understand the results properly, they could choose to stop getting tested for things like breast or colon cancer because they didn't have "the gene". And I'm sure we all here know that's not the right conclusion from this--however, everyone doesn't understand that fully.

Some people though are self-medicating based on the results: http://hplusmagazine.com/editors-blog/r ... e-genomics Of course, that person is at least an MD. Others won't be. And there are also already people trying to sell skin care products based on your genes (I refuse to link to them).

And on GINA: yes, there is a law in place. However, it really hasn't been tested yet. And as we see, it doesn't cover all insurance. It also doesn't protect you from other potential misuses of this information. For example, one woman asked me if her landlord could find out if she has bipolar genes. And if they could choose to not rent to you then. I couldn't tell her she was safe.

I'm also curious if we are going to see people worry about their kids having a "gay gene" and acting on that. It has already happened with current testing. Why would we think DTC is immune to that? "Ethicists Charge Doctor With Trying to Prevent Homosexuality in the Womb" by Dennis Thompson recently talked to this. It gave me chills. (not sure link will work well or persist, so wanted to have the title/author there for googling: http://yhoo.it/9MX1Ql)

Dan, you weren't actually who I had in mind. And I believe the genetic libertarian tag was coined by Misha Angrist, its not meant maliciously.

Yes, these companies are regulated by CLIA (although that didn't stop them from screwing up a load of samples), but CLIA is about good laboratory practice policies, storage and handling, that kind of thing. It's clearly FDA's terrain when it comes to diagnosis etc. NIH's GTR isn't going to be the solution to this; they're not a regulatory agency and have no power to compel anyone to enter their data into it, and no real enforcement mechanism to sanction bad actors. FTC probably should have taken a harder line with industry before now, but they're understaffed and have chosen to concentrate on the worst scams.

You know, the industry had the chance to prevent amy of this from happening; if they'd actually followed througgh with their talk about sitting down together to generate industry standards in 2008, I don't think we'd be having this discussion.

Instead the future of personal genomics is probably going to involve getting your sequence from one of a few large companies and then having the analysis done by someone else, probably based offshore, outside FDAs jurisdiction.

I don't know that the iPhone 4 analogy is quite right; the leap from snp chips to WGS is more than an evolutionary step like that between iPhone variants IMO.

dgmacarthur has saved me some time because I endorse just about everything he says. The decisions should be made based on risks and benefits (and benefits go beyond purely "clinical utility"). Most "libertarians" do not say "no regulations" but promote a system that benefits all. The medicine vs. non-medicine is a sterile argument - but according to FDA rules anything that is intended to "prevent disease" is a medical device. Being a medical device though does not mean it needs to have strict regulation, pre market approval or go through doctors only.

With things like BRCA testing the biggest risk comes from a false negative - a true positive can be lifesaving, a false positive causes temporary anxiety, a false negative can be catastrophic, Self examination is promoted by medical organisations as a valid and effective measure for prevention of skin, testicle and breast cancer (there is some debate on the latter though). Self examination vs.personal genetics (DTC or otherwise), which is more likely to yield false negative results?

It is also the case that when a result (genetic or self-examination) yields a positive result no action will be taken without seeing a doctor who will then confirm the result via specific clinical testing. DTC does not mean that a doctor will not be involved when necessary, DTC genetic testing is a sort of very precise self-examination.

The current main genetics companies seem to have very accurate genotyping, I know that some of the other, less transparent, companies do not and future companies may not do so - some oversight and regular "blind" testing would help. The interpretations and algorithms need to be accurate - so some oversight/regulation is needed, more than exists at the moment. This does not mean it needs to go through doctors and does not need heavy and costly regulation - all of what Daniel proposes will be enough.

Also, why is it necessary to have a doctors authorisation for a simple blood test, why is it not enough to go to a registered lab?

Dr JonboyG - agree 100% on the missed opportunity by reputable industry to sort out a good code of practice. If that would have solved the problem then it still can, but it seems they need some "help". The NIH cannot enforce the GTR, but the FDA could couldn't it?

Of course, you're VERY unlikely to find a researcher who's willing to do this for you, unless part of a bona fide study with the proper ethical clearance. Personally I'm happy not knowing what lurks in my genome.

I'm with you. Like I really want to know that I've got a good chance of getting some horrible disease that no one can cure. Ya, I want to worry about THAT until it happens (or doesn't, which is the point really).

This is the part I take issue with "In Beaudet's view, discussions of the implications of genetic testing are inherently medical, and the process of testing needs to be limited to medical practitioners with relevant training."

I'm happy to see some regulation on blatant false advertising but not the actual sequencing. If I have money to blow on some 3rd party testing provider then Beaudet and his enlightened views can go suck it. If someone isn't smart enough to purchase a service from a reputable provider, they're overdue for a hard lesson anyway.

I'd answer your subject title question with "Why not? Unless the whole thing about humans being 99% similar is a conspiracy, or something." It's not like people aren't going to be genetically modifying themselves some time in the future. Babies are genetically modified by some people already. Plus, people might want to know what illnesses they may have in the future, and how to prevent them, and if they can't, well hell, some people aren't fatalists, and would like to know that anyway.

Unless insurance companies do have automatic access to any genome information about yourself that you have seen, the result is going to be health insurance being priced out of the market.

Except, of course, this has already happened, thanks to laws protecting the HIV-positive from being discriminated against for health insurance. So individual health insurance does not exist any longer, only employee group plans.

Of course, though, I want access to my genome. I may wish to construct some cloned body parts for myself. Right now, that wouldn't be practical, of course... but technology marches on.

so we can't use this info due to unreliable health info, but the big insurance companies will be able to use this info to determine health risks? I know the article does not say this, but who are we kidding that they won't?

Count me in the "extremist" category. I don't need the government to "protect" me from knowledge of myself...

No one is keeping you from your DNA. Go speak to Illumina, give them your money, and they'll sequence you. Go enroll for the Personal Genomes Project, they'll sequence you and then release the data under a creative commons license. That's not the issue here, it never has been.

Keith Grimaldi wrote:

Dr JonboyG - agree 100% on the missed opportunity by reputable industry to sort out a good code of practice. If that would have solved the problem then it still can, but it seems they need some "help". The NIH cannot enforce the GTR, but the FDA could couldn't it?

I'm not really sure. I don't know if they'd want to rather than keeping it in house.

Some day you'll be able to buy a cellphone-sized device under $1,000 that can collect and process all the data you need a lab for today. How will anyone control people's access to their own genome if they can't effectively control illegal downloads, nuclear proliferation, or the drug trade? Yes, hardware is easier to control than software, but not once blueprints are available on the Net and you can build your own out of a biotechnology and electronics hobby set.

Sorry, just realised my last comment was unnecessarily snarky; the environment in this comment thread is pretty toxic...

"You know, the industry had the chance to prevent amy of this from happening; if they'd actually followed througgh with their talk about sitting down together to generate industry standards in 2008, I don't think we'd be having this discussion."

I fully agree that the 2008 meeting was a massive missed opportunity. However, it would also have been possible for other agencies to step in and help the industry out: Linda Avey said in a comment on my blog that Muin Khoury from the CDC declined an opportunity to help out in the area of deciding on standards for background disease risk estimates, for instance. The FDA has also failed to provide any serious guidance, apart from saying "go for it" back in 2008, followed by "you guys are dangerous and need to be shut down" in 2010.

"I don't know that the iPhone 4 analogy is quite right; the leap from snp chips to WGS is more than an evolutionary step like that between iPhone variants IMO."

Well, yes and no. In terms of the sheer scale of data, yes. But in terms of genuinely useful information, the utility of WGS will increase only marginally faster than the utility of new generations of SNP chips, because utility right now is not so much a function of the technology as of the accuracy of the external annotation.

In 2012 it will be affordable to get a WGS. However, it will also probably be just as cheap to run a 50M chip targeting all known SNPs and CNVs with a frequency above 0.5%, as well as most common small indels, as well as every known disease-causing mutation. This will obviously miss variants that are private to you, but it will capture virtually everything that actually has useful health-related annotation associated with it; and the per-base accuracy will almost certainly be higher for a chip than a WGS.

Don't get me wrong - I'm planning to get my genome sequenced ASAP. But I'll be doing so not because I think it will give me a huge amount of useful information I can't get from a chip, but just because I think it will be AWESOME.

Right, the ASAP bit is the kicker: how soon will the price/sequence quality trade-off be good enough to justify forking out? I'm currently looking at around 6-12m as a realistic horizon, but it could be sooner (I'm watching the Illumina/Complete Genomics war with considerable interest).

The contents of my genome are a simple sequence of base pairs. Certainly you can argue that I have a right to that basic data, but that's not what these "services" provide. They provide interpretation of the data that they are in many cases not competent to perform, so it's essentially fraud.

Interpretation is not fraud. They just ought to state confidence levels. And a good service will update your results as more knowledge is obtained.